JP-A 104572/1990 has disclosed that the compounds represented by the following formula A! exhibit gastrointestinal motility enhancing activity and are useful as antiemetic agent or gastrointestinal motility enhancing agent: ##STR2## in which R.sub.1 signifies lower alkyl, or optionally substituted aryl (lower) alkyl,
R.sub.2 signifies hydroxy, alkoxy, alkenyloxy, cycloalkyloxy or substituted alkoxy (the substituent being halogen, hydroxy or oxo), PA1 R.sub.3 signifies amino, disubstituted amino or acylamino, PA1 R.sub.4 signifies halogen, or R.sub.3 and R.sub.4 may together form --NH--N.dbd.N--, PA1 R.sub.5 signifies hydrogen or lower alkyl, PA1 X signifies single bond or lower alkylene, PA1 Y signifies single bond or a group expressed by --CH.sub.2 --, --O--, --S--, --SO--, --SO.sub.2 -- or --NR.sub.6 --, PA1 where R.sub.6 signifies lower alkyl or optionally substituted aryl (lower) alkyl; or may form ethylene together with R.sub.1, PA1 n is 0 or 1, and PA1 the broken line signifies a double bond which may be present when Y is --CH.sub.2 -- and n is 0, provided: PA1 (iii) when Y is a single bond or --CH.sub.2 -- and n is 0, R.sub.1 is an optionally substituted aryl (lower) alkyl; and PA1 n is 1, 2 or 3, and PA1 the wavy line () signifies that configuration of the substitutents on the carbon atom bound to the N-atom in the amide moiety is racemic (RS) or optically active (R or S)!.
(i) when Y is --NR.sub.6 -- or a single bond, n is 0; PA2 (ii) when Y is --O--, n is 1; PA2 (iv) when n is 0, X signifies a lower alkylene!.
Said JP-A-104572/1990, however, contains no specific disclosure about the compounds of the present invention which are represented by the later-appearing formula (I) which concurrently possess 1H-benzotriazole skelton and a nitrogen-containing 7-, 8- or 9-membered aliphatic ring, in particular, their optically active compounds and their pharmacological activities of optically active compounds.
JP-A-83737/1977 discloses that the compounds expressed by the following formula B! exhibit potent activity of reducing the conditioned avoidance response, the apomorphine-induced stereotyped behavior response and the methamphetamine-induced stereotyped behavior, and hence are useful as CNS depressants, in particular, as anti-psychotic drugs: ##STR3## (in which A--CO signifies 4-amino-5-chloro-2-methoxybenzoyl, 5-ethylsulfonyl-2-methoxybenzoyl or 2-methoxy-4,5-azimidobenzoyl group; B signifies allyl or optionally substituted benzyl group; and m is 1 or 2).
Furthermore, JP-A-100473/1977 discloses the compounds represented by the formula C! below: ##STR4## (in which R.sup.1 signifies a lower alkoxy, R.sup.2 signifies an optionally substituted benzyl, and m is 1 or 2).
In these compounds represented by above formula B! or C!, however, the ring bound to the amide moiety (--CONH--) is 5- or 6-membered, and the ring-constituting nitrogen atom is substituted with allyl or benzyl group, and in those points differ from the structure of the compounds represented by the later-appearing formula (I) of the present invention. Moreover, their pharmacological activity again differs from those of the compounds of the present invention.
On the other hand, 4-amino-5-chloro-N-2-(diethylamino)ethyl!-2-methoxybenzamide generic name: metoclopramide; cf. Merck Index, 11th ed. 6063 (1989)! is known as having antiemetic activity and gastrointestinal motility enhancing activity concurrently, and has been used of old for treatments and prophylaxis of functional disorders of gastrointestinal tract, which are associated with various diseases and therapeutical treatments, as gastrointestinal motility enhancing agent. Metoclopramide, however, possesses CNS depressant activity derived from its dopamine D.sub.2 receptor antagonistic activity, which is a drawback for its clinical use. Accompanying the increasing complexity of life in human society and population of aging people, patients suffering from symptoms associated with gastrointestinal dysfunctions also are increasing, and for their treatments development of a compound or compounds exhibiting less CNS depressant activity while having concurrently excellent antiemetic activity and gastrointestinal motility enhancing activity are in demand.